The possibility to study the early physiological responses to TMS stimulation may have valuable implications for both clinical and experimental purposes, providing information about the early direct cortical response of the stimulated areas.
Recent developments in neuroscience have emphasised the importance of integrated distributed networks of brain areas for successful cognitive functioning. Our current understanding is that the brain has a modular organisation in which segregated networks supporting specialised processing are linked through a few long-range connections, ensuring processing integration. Although such architecture is structurally stable, it appears to be flexible in its functioning, enabling long-range connections to regulate the information flow and facilitate communication among the relevant modules, depending on the contingent cognitive demands. Here we show how insights brought by the coregistration of transcranial magnetic stimulation and electroencephalography (TMS-EEG) integrate and support recent models of functional brain architecture. Moreover, we will highlight the types of data that can be obtained through TMS-EEG, such as the timing of signal propagation, the excitatory/inhibitory nature of connections and causality. Last, we will discuss recent emerging applications of TMS-EEG in the study of brain disorders.
A recent study by Conde, Tomasevic et al. (2019) [1] puts a spotlight on the subtleties of experimental design and analysis of studies involving TMS-evoked EEG potentials (TEPs), specifically focusing on the challenge of disentangling genuine cortical responses to TMS from those resulting from concomitant sensory activation. This is a relevant topic that the TMSeEEG community has previously identified [2] and addressed with different strategies [3e6]. Based on the similarity of the evoked EEG responses they obtained in real TMS at different sites and in sham conditions (auditory and somatosensory scalp stimulation), the authors of [1] inferred that TEPs can be significantly contaminated by the effects of concurrent, non-transcranial stimulation.We acknowledge this is a valuable reminder to the TMS-EEG community; however, we contend that another fundamental implication of the work by Conde, Tomasevic and colleagues [1] -only incidentally mentioned at the end of their discussion e is that the evoked responses they obtain from both real TMS and sham conditions are substantially different from the TEPs reported in many of the previous studies (see, for example [7e11]). This discrepancy offers a timely opportunity to focus on the issue of the reproducibility of TEPs across laboratories and, most important, can encourage a constructive debate within the whole TMSeEEG community towards the optimization of shared procedures to obtain genuine responses to TMS.In this vein, Fig. 1 directly compares the TEPs reported in Ref.[1] with others previously published in different studies taken as a reference by Conde, Tomasevic and colleagues [1].The inspection of Fig. 1 clearly shows that it is possible to effectively trigger high-amplitude, sharply rising early (<50 ms) components and overall TEP wave-shapes that are specific for the angle and site of stimulation and that are very different from those obtained in Ref. [1]. This simple comparison highlights a general problem of reproducibility and offers an excellent opportunity to discuss two critical steps in TMSeEEG data acquisition: (i) maximising the impact of TMS on the cortex, and (ii) minimizing EEG confounding factors due to sensory co-stimulation.Regarding the impact of TMS on the cortex, it is very likely that the authors of [1] were not as effective as other investigators for the following reasons. First, they applied TMS with a maximum electric field (E-field) intensity between 70 and 90 V/m according to their estimation, assuming a priori that this would have warranted effective cortical activation based on a previous work [12]. However, in Ref. [1] the authors adopted a small coil (outer winding diameter: 45 mm) which, compared to the larger ones (outer winding
It has been theorized that hemispheric dominance and more segregated information processing have evolved to overcome long conduction delays through the corpus callosum (transcallosal conduction delay-TCD) but that this may still impact behavioral performance, mostly in tasks requiring high timing accuracy. Nevertheless, a thorough understanding of the temporal features of interhemispheric communication is lacking. Here, we aimed to assess the relationship between TCD and behavioral performance with a noninvasive directional cortical measure of TCD obtained from transcranial magnetic stimulation (TMS)evoked potentials (TEPs) in the motor system. Twenty-one healthy right-handed subjects were tested. TEPs were recorded during an ipsilateral silent period (iSP) paradigm and integrated with diffusion tensor imaging (DTI) and an in-phase bimanual thumb-opposition task. Linear mixed models were applied to test relationships between measures. We found TEP indexes of transcallosal communication at~15 ms both after primary motor cortex stimulation (M1-P15) and after dorsal premotor cortex stimulation (dPMC-P15). Both M1-and dPMC-P15 were predicted by mean diffusivity in the callosal body. Moreover, M1-P15 was positively related to iSP. Importantly, M1-P15 latency was linked to bimanual coordination with direction-dependent effects, so that asymmetric TCD was the best predictor of bimanual coordination. Our findings support the idea that transcallosal timing in signal transmission is essential for interhemispheric communication and can impact the final behavioral outcome. However, they challenge the view that a short conduction delay is always beneficial. Rather, they suggest that the effect of the conduction delay may depend on the direction of information flow.
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